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Cancer Immunology, Immunotherapy

, Volume 66, Issue 3, pp 391–401 | Cite as

Bio-HMGB1 from breast cancer contributes to M-MDSC differentiation from bone marrow progenitor cells and facilitates conversion of monocytes into MDSC-like cells

  • Zhaoliang Su
  • Ping Ni
  • Peng She
  • Yueqin Liu
  • Seidu A. Richard
  • Wenlin Xu
  • Haitao Zhu
  • Jia Wang
Original Article

Abstract

Myeloid-derived suppressor cells (MDSC) constitute the major cell population that regulates immune responses. They are known to accumulate in tumors, chronic inflammatory and autoimmune diseases. Previous data indicate that high mobility group box 1(HMGB1) facilitates MDSC differentiation from bone marrow, suppresses NK cells, CD4+ and CD8+ T cells and is involved in cancer development. However, it remains unclear what potential mechanisms of HMGB1 facilitate MDSC differentiation. In the present work, we clearly demonstrate that HMGB1 secreted by cancer cells is N-glycosylated at Asn37, which facilitates monocytic (M)-MDSC differentiation from bone marrow via the p38/NFκB/Erk1/2 pathway and also contributes to conversion of monocytes into MDSC-like cells; HMGB1 blockade by a monoclonal antibody against the HMGB1 B box obviously reduced the accumulation of M-MDSC in tumor-bearing mice, delaying tumor growth and development; additionally, MDSC expansion and HMGB1 up-regulation were also found in breast cancer patients. All these data indicate that HMGB1 might be a potential tumor immunotherapy target.

Keywords

N-glycosylation HMGB1 MDSC Breast cancer 

Abbreviations

Arg-1

Arginase-1

bio-HMGB1

HMGB1 purify from the MCF-7 cell culturing (FBS free) supernatant

ECL

Electrochemiluminescence

EP

Ethyl pyruvate

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

G-MDSC

Granulocytic-MDSC

HMGB1

High mobility group box 1

IMCs

Immature myeloid cells

iNOS

Inducible nitric oxide synthase

LAL

Limulus amebocyte lysate

mAb

Monoclonal antibody

MCF-7

Human breast cancer cell line

M-MDSC

Monocytic-MDSC

PNGase

Peptide N-glycosidase

PVDF

Polyvinylidene difluoride

RAGE

Advanced glycation end-products

rHMGB1

Recombinant HMGB1

S-A

MCF-7 cell culturing supernatant anti-HMGB1 B box mAb

SD

Standard deviation

S–E

MCF-7 cell culturing supernatant with EP

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81370084, 81502663), the Social Development Foundation of Jiangsu Province (Grant No. BE2015668). The six talent peaks project in Jiangsu Province (2013-WSN-002, 2015-WSN-005); the maternal and child project in Jiangsu Province (F201511). We thank Huaxi Xu and the International Science Editing Company for editing and proofreading the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

262_2016_1942_MOESM1_ESM.pdf (457 kb)
Supplementary material 1 (PDF 456 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Zhaoliang Su
    • 1
    • 2
  • Ping Ni
    • 2
  • Peng She
    • 2
  • Yueqin Liu
    • 1
  • Seidu A. Richard
    • 2
  • Wenlin Xu
    • 1
  • Haitao Zhu
    • 3
  • Jia Wang
    • 1
    • 2
  1. 1.The Central LaboratoryThe Fourth Affiliated Hospital of Jiangsu UniversityZhenjiangChina
  2. 2.Department of ImmunologyJiangsu UniversityZhenjiangChina
  3. 3.The Central LaboratoryThe Affiliated Hospital of Jiangsu UniversityZhenjiangChina

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